RESUMEN
Gemcitabine-induced thrombotic microangiopathy (GITMA) is a rare but severe complication seen in cancer patients on gemcitabine therapy. This case report describes a 45-year-old female with metastatic cholangiocarcinoma on gemcitabine-capecitabine who developed acute kidney injury and hypertension without typical hematologic signs of thrombotic microangiopathy (TMA). Despite initial management targeting hypertensive urgency and acute kidney injury, renal function continued to decline and progressed to end-stage renal disease requiring hemodialysis. Laboratory tests revealed TMA features such as elevated lactate dehydrogenase (LDH), decreased haptoglobin, and schistocytes. Renal biopsy confirmed TMA with chronic features. This case highlights the challenge of diagnosing drug-induced TMA without typical hematologic findings.
RESUMEN
Background: Gemcitabine is a broadly used chemotherapeutic agent that can cause a rare but life-threatening complication called thrombotic microangiopathy (TMA). Early recognition is crucial as therapy options are limited. Case Description: We report the case of a 46-year-old patient with pancreatic adenocarcinoma who presented with severe anemia and thrombocytopenia as well as acute kidney injury. A diagnosis of gemcitabine-induced TMA was made. He became rapidly transfusion and dialysis dependent. Despite discontinuation of gemcitabine and treatment with high-dose corticotherapy as well as plasmapheresis, no improvement in both renal and hematological parameters was seen. Treatment with eculizumab was initiated. One week after the first administration, the patient no longer required packed cells nor platelet transfusions and one month later, dialysis could be discontinued. After five doses, treatment with eculizumab was stopped. Four months later, his serum creatinine was 1 mg/dL. Conclusions: This case report illustrates the promising beneficial effects of eculizumab in gemcitabine-induced TMA, both regarding transfusion dependence as well as improvement in renal function, thereby allowing further therapy options in patients with an active malignancy.
RESUMEN
BACKGROUND: Gemcitabine is a broadly prescribed chemotherapy, the use of which can be limited by renal adverse events, including thrombotic microangiopathy (TMA). METHODS: This study evaluated the efficacy of eculizumab, a monoclonal antibody targeting the terminal complement pathway, in patients with gemcitabine-induced TMA (G-TMA). We conducted an observational, retrospective, multicenter study in 5 French centres, between 2011 and 2016. RESULTS: Twelve patients with a G-TMA treated by eculizumab were included. The main characteristics were acute renal failure (100%), including stage 3 acute kidney injury (AKI, 58%) and renal replacement therapy (17%), hypertension (92%) and diffuse oedema (83%). Eculizumab was started after a median of 15 days (range 4-44) following TMA diagnosis. A median of 4 injections of eculizumab was performed (range 2-22). Complete hematological remission was achieved in 10 patients (83%) and blood transfusion significantly decreased after only one injection of eculizumab (median of 3 packed red blood cells (range 0-10) before treatment vs 0 (range 0-1) after one injection, P < 0.001). Two patients recovered completely renal function (17%), and 8 achieved a partial remission (67%). Compared to a control group of G-TMA without use of eculizumab, renal outcome was more favourable. At the end of the follow up, median eGFR was 45 vs 33 ml/min/1.73m2 respectively in the eculizumab group and in the control group. CONCLUSIONS: These results suggest that eculizumab is efficient on haemolysis and reduces transfusion requirement in G-TMA. Moreover, eculizumab may improve renal function recovery.
Asunto(s)
Lesión Renal Aguda , Anticuerpos Monoclonales Humanizados/administración & dosificación , Microangiopatías Trombóticas , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/terapia , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/uso terapéutico , Transfusión Sanguínea/métodos , Transfusión Sanguínea/estadística & datos numéricos , Inactivadores del Complemento/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Femenino , Francia/epidemiología , Humanos , Pruebas de Función Renal/métodos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Inducción de Remisión/métodos , Terapia de Reemplazo Renal/métodos , Microangiopatías Trombóticas/diagnóstico , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/terapia , Resultado del Tratamiento , GemcitabinaRESUMEN
A 47-year-old male with stage IV pancreatic cancer developed gemcitabine-induced thrombotic microangiopathy (GiTMA) after treatment with gemcitabine and nab-paclitaxel. GiTMA is a rare and life-threatening complication with an incidence ranging from 0.015% to 1.4% and reported mortality rate ranging from 50% to 90%. Clinically, GiTMA manifests as microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. Early identification of GiTMA is essential to initiate early treatment and improve survival. Treatment of GiTMA includes discontinuation of gemcitabine, along with initiation of steroids, therapeutic plasma exchange (TPE), rituximab, and eculizumab. To our knowledge, this is the first case of GiTMA treated with ravulizumab, a long-acting complement inhibitor. Given the increasing number of patients treated with gemcitabine and seriousness of this complication, it is important for physicians to be aware of this disease entity and maintain a high index of suspicion when evaluating patients with microangiopathic hemolytic anemia, thrombocytopenia, and renal failure.